TMEM231为跨膜蛋白，在肿瘤中未有研究。我们前期发现TMEM231表达与胃癌化疗抵抗正向相关。机制初步显示TMEM231表达能激活PI3K/AKT/NF-κB信号通路，上调PFKFB2，增强Warburg效应。POSTN为基质分泌性蛋白，与化疗抵抗密切相关，机制分析发现同样激活PI3K/AKT/NF-κB通路，上调PFKFB2，增强Warburg效应。Co-IP发现TMEM231和POSTN存在相互结合。ChIP初步显示NF-κB p65可与PFKFB2启动子结合。因此后续研究需明确：TMEM231作为候选癌基因，介导POSTN激活PI3K/AKT通路，进而诱导NF-κB p65转录刺激PFKFB2表达，从而增强Warburg效应促进化疗抵抗。该项目顺利完成不但能阐明TMEM231在化疗抵抗中的作用，同时进一步明确POSTN通过TMEM231相互作用参与胃癌细胞化疗抵抗的重要调控机制。

The role of TMEM231, a transmembrane protein, was not studied in tumor. Our recent results showed that TMEM231 expression was associated with chemoresistance in patients with gastric cancer. We noticed that TMEM231 could activate the PI3K/AKT/NF-κB signaling pathway, up-regulate PFKFB2, and enhance the Warburg effect. POSTN, a secretory protein of extracellular matrix, plays an important role in chemoresistance. POSTN could also activate the PI3K/AKT/NF-κB signaling pathway, up-regulate PFKFB2, and enhance the Warburg effect. Co-IP showed TMEM231 and POSTN had mutually combination. ChIP showed that NF-κB p65 could bind to the promoter region of PFKFB2. Therefore, the follow-up studies need to clear: TMEM231, as a candidate oncogene, mediates POSTN to activate the PI3K/AKT signaling pathway, and then induce NF-κB p65 to stimulate the transcription of PFKFB2, and finally enhance Warburg effect and promote chemoresistance. The study will elucidate the key role of TMEM231 in chemoresistance and further clarify the regulatory mechanism that POSTN involves in chemoresistance of gastric cancer cells through interacting with TMEM231.